A prostate cancer specific nuclear matrix protein (NMP). PC-1. has been identified (1). Matritech scientists have produced a number of monoclonal antibodies to PC-1 and have characterized the antibodies by immunofluorescence staining of human adenocarcinoma cells showing nuclear localization with a punctate staining pattern. The antibodies have also been shown to react with PC-1 by two dimensional western immunoblot analysis. The goal of this SBIR Phase I research is to characterize PC-1 at the molecular level and investigate its role in prostate cancer cell function using an in vitro model of human prostate cancer. Monoclonal antibodies to PC-1 will be used to screen a lambda gtll cDNA library from a tissue source known to express PC-1. Clones identified from the screen will be characterized on the basis of protein coding potential, (theoretical molecular weight and pI) as well as its prostate cancer cell specificity. The DNA sequence of the PC-1 cDNA will be determined. DNA sequence will be used to generate antisense oligonucleotides which will be used to treat cells in a model system of prostate cancer to determine the effect of loss of PC-1 function on cancer cell viability. Oligonucleotide treated cells will be plated in soft agar and the number of colonies capable of anchorage independent growth will be measured by direct counting. Additional surrogate markers of cancer, such as cell growth rate and serum requirements, will also be measured. Appropriate control cancer cell lines lacking PC-1 will also be treated in the same manner. If PC-1 expression is shown to play a critical role in prostate cancer cell viability in the aforementioned model, it will be further investigated as a target for anti-cancer chemotherapy. Antisense oligonucleotides, monoclonal antibodies, or small organic compounds may be developed as cancer specific therapeutic substances in the future. PROPOSED COMMERCIAL APPLICATION: Prostate cancer is the second leading cause of death among males with increasing numbers of new cases reported each year. PC-1 may be a prostate cancer specific therapeutic target. Demonstration of its essential role in the life cycle of prostate cancer cells would validate PC-1 as a target for development of antagonist compounds. This could lead to the development of new therapeutics for the treatment of prostate cancer with greater tumor specificity and therefore fewer side effects.